We have defined propagable, quantifiable differences between normal and rheumatoid synovial cells in tissue culture, and shown them to be at least partly due to an "activator" peptide (CTAP), present in excess in rheumatoid cells. CTAP initiates a process (activation) which includes increased energy metabolism and marked stimulation of hyaluronic acid synthesis, both characteristic stigmata of chronic rheumatoid synovitis. These actions of CTAP, and its widespread cellular distribution, qualify it for a role as a key regulator of inflammation, modifying progression from the exudative to the reparative phase. Measurements of CTAP in simple inflammation show an early peak of activity, and continued excess of CTAP was shown to produce the biochemical activities characteristic of chronic rheumatoid inflammation. The objectives of this proposal are: A. To study the mediator substance (CTAP): (1) By isolation of CTAP. (2) By chemical characterization of CTAP. B. To study the connective tissue activation process: (1) By elucidating the mechanism of action of CTAP. (2) By studying formation, release, and degradation of CTAP. (3) By determining tissue localization and concentration of CTAP in rheumatic diseases and in model systems. (4) By searching for novel ways (drugs) to interdict the chronic inflammatory process using the activated synovial cell culture as a model system. BIBLIOGRAPHIC REFERENCES: Castor, C. W. and Yaron, M: Connective tissue activation. VIII. The effects of temperature studies in vitro. Arch. Phys. Med. Rehab. 57:5-9, 1976. Castor, C. W.: "Joint Structure and Function" and "Osteoarthritis." In 22ND Rheumatisim Review, edited by W. M. Mikkelsen, 1976, in press.